3.2 Intervertebral space height
There were no significant differences in intervertebral space height among the groups immediately and at 3, 6, and 12 months after operation (P > .05). There was a significant difference in intervertebral space height among the groups immediately and at 3, 6, and 12 months after operation (P > .05) (Table 2).
3.3 Fusion rate
The Williams et al method was used to evaluate the rate of intervertebral fusion. The fusion rate in group A was 16.1% (5/31) at 3 months, 45.2% (14/31) at 6 months, and 71.0% (22/31) at 12 months. In group B, the fusion rate was 43.8% (14/32) at 3 months, 75.0% (24/32) at 6 months, and 93.8% (30/32) at 12 months. In group C, the fusion rate was 40.0% (12/30) at 3 months, 66.7% (20/30) at 6 months, and 86.7% (26/30) at 12 months. Thus, rhBMP-2 + bone allograft fusion rate was the highest, while the fusion rate in the autologous bone marrow + bone allograft group was higher than that of pure bone allograft (Table 2, Fig. 2).
3.4 Clinical efficacy
There were 15 cases of thigh numbness in segments L4–L5 in the 3 groups immediately after operation, which did not require special treatment and disappeared 2 weeks after operation. In the 3 groups, the VAS scores of low back pain and leg pain and the ODI scores at 3, 6, and 12 months after surgery were significantly improved compared with the preoperative scores (P < .05). The VAS and ODI scores in groups B and C were significantly higher than those in group A (P < .05), but there was no significant difference between groups B and C (P > .05) (Table 3).
As a procedure with increasing popularity, XLIF differs from the traditional posterior or anterior/anterior approaches, involving a lateral approach. Aiming to protect the nerve, it allows full resection of the intervertebral disc and provides an excellent environment for fusion; also having a good indirect decompression effect. However, whether cage stand-alone can provide reliable and lasting stability to maintain intervertebral space height without affecting the fusion between vertebral bodies is also a problem in XLIF. Patients included in this study were all treated with cage stand-alone without assistant internal fixation system. Because the anterior longitudinal ligament, posterior longitudinal ligament, and facet joints are retained, multidirectional motion can be stabilized by the tension of the residual ring and ligament. In addition, biomechanical analysis suggests larger fusion cages can provide higher segmental stability. Some studies also suggest stand-alone may be a better choice in the absence of osteoporosis, severe segmental instability, or partial bone defects. Marchi and coworkers have argued some patients with facet joint lesions need assisted posterior screw-rod fixation because moderate to severe facet joint degeneration indicates these joints are under heavy load or exercise. Therefore, patients included in this study had no obvious degeneration of segmental instability, no osteoporosis or bone destruction, no obvious facet joint lesions, and no endplate injury. Assisted posterior nail-rod fixation increases the risk of anesthesia, the need to change body position during operation, and the economic burden of patients.
New materials for intervertebral bone grafting are in constant development. Although many kinds of bone graft materials are used in clinical, a common important purpose is to achieve early, long, and firm fusion of these materials. The osteoinductive ability of bone substitutes is closely related to bone fusion. rhBMP-2 was first discovered by Uris et al in 1965[11,12]; as a member of the transforming growth factor-beta superfamily, it can induce undifferentiated mesenchymal cells to differentiate into osteoblasts and chondrocytes, and promote their proliferation. It can also promote the differentiation and maturation of osteoblasts, and has strong osteogenic induction effects. Studies have shown rhBMP and bone graft has better fusion effects. A multicenter study showed that rhBMP-2 was used in 143 patients with lumbar disc herniation during lumbar fusion. After 2 years of follow-up, the final fusion rate was 94.5%, higher than 88.7% in the control group. Boden et al also showed that rhBMP-2 was more effective than iliac bone graft. Nevertheless, some studies have reported complications such as osteolysis, heterotopic bone formation, and cage settlement or displacement.[16,17] Some studies have also shown these complications may be dose-dependent. No serious complications were found in this study. Therefore, low-dose rhBMP-2 appears to be relatively safe. Some studies have also shown the addition of bone marrow to bone graft materials can promote fusion, as osteogenic progenitor cells have a strong ability to induce bone, and the bone marrow is one of the most abundant and reliable sources of osteoblasts.
According to the CT evaluation at 3, 6, and 12 months after operation, the fusion rate of the bone marrow + allograft group was higher than that of bone allograft alone, while rhBMP-2 + allograft as bone graft material had the highest fusion rate among the 3 groups. Long-term follow-up studies have found failure to achieve osseous fusion between vertebral bodies can lead to instability of the spine, degeneration of the vertebral body, and increased risk of reoperation. Relevant studies have also indicated rhBMP-2 can significantly reduce surgical revision rate. In this study, cage displacement only occurred in 1 patient who used allogenic bone at 3 months after operation, and cage removal and fusion and internal fixation were performed in the later stage (Fig. 1). The patients recovered well after operation. We believe this case of cage displacement was related to slow fusion and inappropriate postoperative activity.
In this study, the VAS and ODI scores at 3, 6, and 12 months after operation were significantly improved in each group compared with those before operation (P < .05). The excellent and good rates of VAS and ODI scores in groups B and C were significantly higher than in group A (P < .05), but there was no significant difference between groups B and C (P > .05). In summary, the application of allogenic bone in combination with bone marrow or rhBMP was associated with enhanced early postoperative improvement after XLIF in comparison with allogenic bone alone, with no significant difference between the 2 alternatives. However, this study did not compare the clinical effects of the 3 groups at long term. Assessment of the final clinical effects of the 3 groups requires a longer follow-up study.
We found intervertebral space height improved significantly in all groups; decreasing slightly at 3, 6, and 12 months after operation in comparison to immediately after operation, but without symptoms and no significant difference among the 3 groups (P > .05). Research has shown rhBMP has a significant osteolytic effect, leading to dissolution of the endplate, thereby increasing cage sedimentation rate and reducing the intervertebral space height. However, no significant differences were found regarding intervertebral space height among the 3 groups. This may be one of the advantages of XLIF compared with other spinal fusion operations. A larger cage can be implanted into the opening system of the approach, spanning the entire vertebral body width, so that the cage can ride across the strongest epiphyseal ring on both sides of the vertebral body to restore intervertebral space height. The load stress of the endplate is dispersed, thus the settlement of the cage is reduced. Marchi and coworkers consider the small settlement of cage does not affect the fusion rate and clinical effects. However, we believe the assisting internal fixation system remains an effective way to stabilize the spinal segment and avoid cage collapse and displacement.
In this study, we assessed the BMI of the included cases, finding significant differences in the surgical effects and fusion rates between obese patients and nonobese patients. Nevertheless, during the operation, obesity may pose a difficulty, due to the depth of operation site, poor illumination, low clarity of the operation field, and complicated operation of the endplate.
This study shows the use of rhBMP-2 + allogenic bone as fusion material in XLIF can achieve higher fusion rates and better clinical effects than that of bone allograft alone and bone marrow + allogenic bone in early stages. Although the clinical effect of bone marrow + allogeneic bone is comparable to that of rhBMP-2 + allogeneic bone, bone marrow extraction during operation requires puncture from iliac bone, which increases the risk of infection and pain, and has inferior fusion effects in comparison to rhBMP-2 + allogeneic bone.
In this study, although the combination of allogeneic bone and rhBMP-2 can achieve higher fusion rate and better clinical efficacy in XLIF, there is no detailed large sample study on the possible complications of allogeneic bone + rhBMP-2 in XLIF. Secondly, rhBMP-2 causes the settlement of fusion cage in other fusion operations. Whether it will affect the clinical effect after XLIF remains to be further studied. In addition, the sample size of this study is small, and long-term large sample size research and observation follow-up are needed.
In conclusion, the application of rhBMP-2 + allogeneic bone as bone graft material in extreme lateral interbody fusion (XLIF) can achieve higher fusion rate and better clinical results.
Conceptualization: Wei Zhang.
Data curation: Yuan Gao, Jiaqi Li, Hao Cui.
Formal analysis: Yuan Gao, Yapeng Sun, Zeyang Li, Wenyuan Ding, Yong Shen.
Methodology: Yuan Gao, Fei Zhang.
Writing – original draft: Yuan Gao.
Writing – review & editing: Wei Zhang.
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Keywords:Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
bone graft materials; extreme lumbar interbody fusion; fusion rate; rhBMP-2